Long-Term IL-2 Incubation-Induced L-type Calcium Channels Activation in Rat Ventricle Cardiomyocytes
- 53 Downloads
The following study examined the impact of IL-2 on Ca2+ channel activity in the event of several hours’ incubation in IL-2. The right ventricle free wall for action potential measurements was isolated and perfused with Tyrode solution. The whole-cell voltage clamp experiments were performed on enzymatically isolated single cardiomyocytes. The whole-cell voltage clamp recording of Ca2+ currents was performed using the Cs+-based pipette and bath solutions. The protocol with depolarizing prepulse (− 40 mV) was used to inactivate both Na+ current and Ca2+T-type current. The L-type Ca2+ current was elicited by a series of 250 ms depolarizing square pulses with 10 mV increments. At the 15th minute of continuous recording, the peak density at 0 mV was − 3.036 ± 0.3015 pA/pF under IL-2 and − 3.008 ± 0.3452 pA/pF in control conditions. The IL-2 in moderate concentration (1 ng/mL) has no acute effects on ICa.L in rat ventricular cells. In contrast, to the lack of acute effects, the long-term incubation with IL-2 (2 h or more) produced a prominent enhancement of Ca2+L-type current. In rat, ventricular myocardium IL-2 (1 ng/mL) produced a very gradual prolongation of subendocardial APs which reached a maximal extent after 3–4 h of treatment. The patch clamp study shows an IL-2-induced ICa.L current activation, while the action potential studies on multicellular ventricular preparations suggest an IL-2-induced L-type Ca2+ channel participation in the development of AP.
KeywordsInterleukin 2 L-type Ca2+ current (ICa.L) Action potential duration (APD) Right ventricle Heart Rat
This work was supported by the Russian Science Foundation.
All authors contributed toward data analysis, drafting, and revising the paper and agree to be accountable for all aspects of the work.
The present study was supported by a grant from the Russian Science Foundation (Grant No. 16-14-10372).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 1.Arai, K., Nishida, J., Hayashida, K., Hatake, K., Kitamura, T., Miyajima, A., et al. (1990). Coordinate regulation of immune and inflammatory responses by cytokines. Rinsho Byori, 38, 347–353.Google Scholar
- 4.Cao, C. M., Xia, Q., Bruce, L. C., Zhang, X., Fu, C., & Chen, J. Z. (2003). Interleukin-2 increases activity of sarcoplasmic reticulum Ca2+-ATPase, but decreases its sensitivity to calcium in rat cardiomyocytes. Journal of Pharmacology and Experimental Therapeutics, 306, 572–580.CrossRefGoogle Scholar
- 8.Cao, C. M., Xia, Q., Bruce, I. C., Zhang, X., Fu, C., & Chen, J. Z. (2003). Interleukin-2 increases activity of sarcoplasmic reticulum Ca2+-ATP-ase, but decreases its sensitivity to calcium in rat cardiomyocytes. Journal of Pharmacology and Experimental Therapeutics, 306, 572–580.CrossRefGoogle Scholar
- 17.Ovchinnikov, R. S., Mitrokhin, V. M., & Mladenov, M. I. (2015). Effects of vascular endothelial growth factor β on the bioelectric activity of rat atrial myocardium under normal conditions and during gradual stretching. Journal of Biological Regulators & Homeostatic Agents, 29, 835–840.Google Scholar
- 20.Li, X. Q., Zhao, M. G., Mei, Q. B., Zhang, Y. F., Guo, W., Wang, H. F., et al. (2003). Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes. Acta Pharmacologica Sinica, 12, 1224–1230.Google Scholar
- 26.Ha, K. C., Kwak, Y. G., Piao, C. S., Chae, H. J., & Chae, S. W. (2007). Differential effects of superoxide radical on the action potentials in ventricular muscles, Purkinje fibers and atrial muscles in the heart of different aged rats. Archives of Pharmacal Research, 30, 1088–1095.CrossRefGoogle Scholar